Antibodies to human papillomavirus (HPV) primarily recognize surface exposed residues on five loops of the major capsid protein (L1) that vary significantly among HPV types. We determined which loops were required for neutralization for 70 HPV16 specific human monoclonal antibodies (mAbs) cloned from participants who received an HPV vaccine, and we describe molecular features of those antibodies. Chimeric HPV16 pseudovirus (cpsV), each having one surface loop bearing multiple amino acid substitutions, were used to determine neutralization specificity. The HPV16-FG-loop was the loop most frequently required for neutralization (44 of 70, 62.9%), however, all other surface loops were used for neutralization by multiple mAbs: HI (13, 18.6%), DE (15, 21.4%), EF (six, 8.6%), BC (four, 5.7%). Antibodies that required multiple loops were common (17, 24.3%). Three mAbs (4.3%) required sequences on the c-terminus of L1 and for another three mAbs the neutralization specificity could not be determined. Two types of mAbs appeared to be overrepresented: ten mAbs used V H 2-70 IGHV paired with V L λ1-40, having characteristic mutations in complementarity determining region two (CDRL2). Cryogenic electron microscopy (Cryo-EM) revealed that two of these antibodies bound five Fabs per pentamer interacting with all five L1-surface loops. The other type of mAbs that appeared to be overrepresented were ten mAbs using V H 4-34, seven of which also used D H 3-16*02 with conserved CDRH3 sequences. Cryo-EM for one of these mAbs, that required the FG-loop for neutralization, was shown to bind one Fab per pentamer at the apex, interacting with the DE- and FG-loops, with sequences of the Fab CDRH3 inserted between the DE- and FG-loops from two protomers. These two types of mAbs were found repeatedly in the four participants suggesting that these antibodies shared developmental pathways and bound to similar immunodominant epitopes on the virus.

Most human mAbs recognized L1 surface loops but three of 70 recognized sequences on the C-terminal arm of L1Some antibodies induced by HPV vaccination follow shared developmental pathways. Human monoclonal antibodies using V H 2-70/V L λ1-40 were found in all participants and bound with at a stoichiometry of five Fabs per capsomer. Human monoclonal antibodies using the diversity gene segment D3-16*02 were found in all participants and one Fab was shown to bind with a stoichiometry of one Fab per capsomer.

A panel of 70 HPV16 specific human monoclonal antibodies (mAbs), cloned from memory B cells or plasmablasts following HPV vaccination, was characterized by determining the surface loops of the major capsid protein (L1) required for neutralization and examined for shared molecular features. All five L1 loops were found to be used for neutralization by one or more antibodies, but the most frequent target of these antibodies was the FG loop followed by the HI and DE loops. Ten antibodies paired the heavy chain variable gene V H 2-70 with the light chain variable gene V L λ1-40 and these antibodies had conserved mutations in the CDRL2 region of V L λ1-40. Mutating the CDRL2 back to the predicted germline sequence significantly reduced neutralization. Cryo-EM analysis of two V H 2-70/V L λ1-40 mAbs showed five Fabs binding per L1 pentamer and a conserved epitope with Fabs interacting with all five variable loops across two adjacent protomers. Seven other mAbs had a heavy chain composed of the variable region V H 4-34 with the diversity gene D3-16*02 resulting in the sequence motif WSGYR in the CDRH3. Mutation of that sequence to alanine ablated HPV16 neutralization activity. A cryo-EM structure of one of these antibodies showed one Fab binding the pentamer apex with the WSGYR motif inserting between three loops from two protomers. Antibodies with paired V H 2-70/V L λ1-40 and the antibodies with CDRH3 containing the WSGYR sequence, were found in all four study participants suggesting that such antibodies may be commonly elicited following HPV vaccination.

Cervical cancer is preventable by following guidelines for vaccination, screening, diagnosis and treatment of preinvasive cervical lesions. We implemented a multicomponent intervention to increase rates of colposcopy after abnormal screening results in three clinic systems in the Rio Grande Valley, along the Texas-Mexico border. The goal of this study was to assess the outcomes of this program including participation in colposcopy within 90 days of screening for women with abnormal screening results, and the time between screening and colposcopy appointments during the first year (Year 1/baseline) and subsequent years (Years 2 through 4) of program implementation.

We performed a retrospective cohort analysis of medical records of clinics participating in the program. We utilized multiple logistic regression and linear regression to assess the colposcopic outcomes of women with indication for colposcopy.

A total of 1556 of the 14,846 (10.5 %) women who had undergone cervical cancer screening had abnormal results and met the criteria to be referred for colposcopy. There was a significant increase in the proportion of women who underwent colposcopy (within 90 days of screening) from Year 1/baseline (82.7 %) to Year 2 (90.6 %), OR= 1.65, p-value< 0.05. Similarly, the mean interval from screening to colposcopy decreased significantly from baseline (79 days) to Year 2 (49 days), to Years 3 and 4 (40 and 41 days, respectively), p < 0.001.

Our results suggest that multicomponent interventions can improve and sustain appropriate and timely colposcopy among women in medically underserved regions, improving cervical cancer prevention efforts in resource-limited settings.

The continued rise in recurrence and mortality rates of cervical cancer suggests the need to find novel therapeutic targets. Previous studies suggest that TRIP4 acts as a transcription factor to regulate cervical carcinogenesis and progression. Our aim was to explore whether the key downstream genes of TRIP4 functions same as TRIP4 in promoting cervical cancer development. We analyzed and confirmed the downstream targets of TRIP4 by RNA sequencing in cervical cancer cells with TRIP4 knockdown. The expression correlation between TRIP4 and GATA2 and the effect of GATA2 on cervical cancer cell growth were determined respectively by Western Blot, Scratch, Spheroid, and MTT analyses. Pulldown and ChIP experiments were performed to analyze the binding of TRIP4 to the promoter of GATA2. The clinical significance of GATA2 and TRIP4 expression in cervical cancer patients was analyzed by tissue microarray staining. GATA2 was highly expressed in cervical cancer tissues. Knockdown of GATA2 inhibited the growth, metastasis and stemness of cervical cancer cells and sensitized cervical cancer cells to radiation therapy. The inhibitory effect of TRIP4 knockdown on cervical cancer cells was rescued by GATA2 overexpression. Furthermore, TRIP4 could bind to the specific GATA2 promoter region, thereby activating its transcription. Clinical tissue microarray analysis indicated that the expression of TRIP4 and GATA2 was positively correlated, and high expression of both predicted a poor prognosis in cervical cancer patients. Our study demonstrated that GATA2 functions as the key downstream target of TRIP4 to promote cervical cancer progression and effective intervention of TRIP4/GATA2 signaling is expected to be developed as potential cervical cancer therapeutic strategy.

High-risk HPV infection is a necessary but not sufficient factor for the development of precancerous lesions and cervical cancer. Beyond mere HPV positivity, the persistence of infection over time plays a crucial role. This study aims to evaluate the clearance and persistence rates of HPV 16 and 18 genotypes.

The cervical cytology results were reported using the 2014 Bethesda System classification. The cervical cytology samples were analyzed using the Roche Cobas® 4800 HPV tests. Patients with any HPV genotype other than 16 or 18, those with missing data, those who were lost to follow-up, those who underwent excisional procedures or hysterectomy, and those with high-grade cervical dysplasia were excluded from this study.

Among 191 patients (mean age: 41.2 ± 0.6 years, 16.8% postmenopausal), the mean follow-up was 21.6 ± 0.7 months. No significant differences were found between the clearance and persistence groups in age, follow-up duration, cervical biopsy, or endocervical curettage results. However, HPV 16 had a higher persistence rate (28.2%), and abnormal cytology was more frequent in the persistence group (p = 0.038).

Around 25% of patients had persistent HPV infection. Close monitoring is essential for those with CIN 1 on initial colposcopy, as they may have a higher risk of progressing to high-grade dysplasia compared to those without dysplasia.

To determine whether intrauterine device (IUD) use is associated with a significantly increased risk of abnormal cervical cytology.

A retrospective cohort study was carried out at the University of Campinas, Campinas, SP, Brazil. Data came from medical records of 2,963 women from a family planning clinic who had undergone at least one cervical cytology for screening between 1990 and 2017. Women were split into three groups: users of either copper (Cu)- or the levonorgestrel 52 mg-IUD (2,305) and users of other contraceptive methods (658). The dependent variable was the cytological results as normal and abnormal, based on the Bethesda System. The most severe cytological result of each participant was considered and when all her results were normal, the last one was considered.

IUD use was associated with a lower risk of abnormal cervical cytology after adjusting for the number of cytology assessments per participant (RR 0.74; 95% CI 0.55;0.99; p = 0.049). Abnormal cervical cytology was more common in women with multiple cytology assessments and a longer duration since sexual debut. For each additional cytology test, the risk increased by 33.8% (p < 0.001), and for every additional year since sexual debut, the risk increased by 6.2% (p < 0.001). A lower incidence of abnormal cervical cytology was observed among women with a history of caesarean delivery, with a 24.9% reduction in risk per additional caesarean (p < 0.001). IUD users underwent more cervical cytology assessments than non-IUD users.

We identified low risk of abnormal cervical cytology among IUD users.

Fertility-sparing treatment (FST) has become a key aspect of managing gynecologic cancers in reproductive-age patients who wish to preserve fertility. Several leading clinical societies, including the European Society of Gynecological Oncology, the European Society for Radiotherapy and Oncology, the European Society of Pathology, and the European Society of Human Reproduction and Embryology, have published evidence-based guidelines on fertility-sparing strategies and post-treatment surveillance of patients with early-stage gynecologic cancers, in particular endometrial and cervical cancers. These guidelines highlight MRI as essential to initial patient selection and follow-up. Properly tailored pelvic MRI protocols and clear MRI reports are key to performing accurate staging, assessing eligibility, and confirming the initial and ongoing feasibility of FST. Accordingly, radiologists, particularly those specializing in gynecologic imaging, play a critical role in the multidisciplinary approach to FST. They should be well-versed in FST eligibility criteria and key MRI findings before and after FST, ensuring these details are comprehensively communicated in structured MRI reports.

Epidemiological and experimental studies have suggested that chronic H. pylori infection may be associated with colorectal cancer (CRC), a topic of growing interest. The Bradford-Hill criteria are the mainstay of the epidemiological approach to causal inference. We aim to evaluate the epidemiological evidence based on the Bradford-Hill causality criteria and the association between H. pylori and CRC.

A literature review of the databases search: Pubmed, ScienceDirect, Embase, SciELO, Cochrane, and Medline. There are no limits in a period. Information sources that were coherent with the objectives set were selected.

Applying the Bradford Hill criteria, we can conclude that H. pylori is positively associated with CRC. The current epidemiological findings should stimulate future studies to explain how H. pylori interacts with intestinal dysbiosis and the role of H. pylori eradication in the treatment and prevention of CRC.

H. pylori reasonably meets the Bradford Hill criteria for causality. Further studies are required to consolidate the data and generate strategies to determine whether H. pylori eradication translates into decreased CRC incidence and mortality in large populations.

Background: Molecular triage testing for high-risk human papillomavirus (hrHPV)-based cervical cancer screening can be used in self-sampling, potentially reducing unnecessary colposcopies and increasing attendance. However, its commercial value remains underexplored. This study used headroom analysis to estimate the maximum reimbursable price (MRP) at which molecular testing would be cost-effective for the triage of hrHPV-positive women, compared with cytology. Methods: A validated microsimulation Markov model for the Dutch cervical cancer screening program evaluated three triage scenarios: (1) cytology (base scenario), (2) molecular testing in self-samples only (scenario I), and (3) molecular testing on self- and GP-collected samples (scenario II). Test sensitivity and specificity ranged from 65% to 95%, with a threshold of EUR 20,000 per life-year gained. Results: In scenario I, MRPs ranged from EUR 244 (85% sensitivity, 75% specificity) to EUR 435 (95% sensitivity, 95% specificity). In scenario II, molecular testing was cost-effective across all parameters, with MRPs from EUR 162 (65% sensitivity, 65% specificity) to EUR 624 (95% sensitivity, 95% specificity). Increasing the sensitivity did not significantly affect life-years gained (due to the low mortality of cervical cancer in the Netherlands), but increased specificity did reduce the number of unnecessary colposcopies. Conclusions: Enhancing the specificity of molecular triage testing will improve its commercial value by reducing colposcopy referrals without affecting the number of life-years gained.

S. haematobium is a recognized carcinogen and is associated with squamous cell carcinoma of the bladder. Its association with high-risk(HR) human papillomavirus (HPV) persistence, cervical pre-cancer and cervical cancer incidence has not been fully explored.

We searched OvidSP MEDLINE, OvidSP Embase, Global Index Medicus, PubMed and the Wiley Cochrane library without date or language restrictions up to April 20, 2024 for abstracts evaluating the association of female genital schistosomiasis (FGS) with the prevalence, incidence or persistence of cervical HR-HPV, and incidence of histology-verified cervical pre-cancer or cancer. Cervical pre-cancer defined using cervical cytology or visual inspection with acetic acid (VIA) was also considered, but as lower quality evidence. We assessed the risk of bias of included studies using a modified Newcastle Ottawa scale. This study is registered on PROSPERO: CRD42023389301.

We identified 1,170 publications and six studies were eligible for inclusion. Five studies were cross sectional and 1 was prospective. The studies describe 1081 women living in sub-Saharan Africa. One study from Zimbabwe reported an increased risk of HR-HPV prevalence at baseline in women with composite-FGS compared to women without FGS (aOR 1.9, 95% CI 1.1 - 3.6, p = 0.03), however no association was seen after 5 years of follow-up. Another study from KwaZulu-Natal reported an increased odds of any HPV prevalence among women with visual-FGS compared to women without FGS (aOR 1.71 [1.14 - 2.56], p = 0.01). However, a study in Madagascar did not show increased odds of any HPV among women with visual-FGS compared to women without FGS (OR 1.0 [0.82 - 1.2). Of 4 studies evaluating the association of FGS and cervical pre-cancer, one reported an increased risk of VIA abnormalities in women with molecular-FGS compared to those without (aOR 6.08, 95% CI 1.58 - 23.37). Three studies did not report an association between FGS and cervical pre-cancer (cytology defined (n = 2) and histology defined (n = 1)).

There are limited and low quality data on the risk of HR-HPV infection and cervical pre-cancer and cancer among women with FGS. Given limited data, it was not possible to confirm or exclude an association between FGS and HPV, cervical pre-cancer, and cervical cancer and additional research is needed.

BackgroundIn the global scenario of public health, cervical cancer poses a major threat with high mortality rates, especially in women. New incidence cases and prevalence vary across different regions, as recently shown by GLOBOCAN data. The development of cervical cancer is primarily due to persistent infection by high-risk genotypes of human papillomavirus (HPV), which is a multifaceted process that is influenced by genetic, environmental, and lifestyle factors.PurposeThe goal of this study is to thoroughly investigate cervical cancer, including its etiology, molecular mechanisms, progression, diagnosis strategies, and current therapies. This review further highlights the transformative power of HPV vaccination and screening programs in curbing the disease's burden and potentially promising novel approaches like immunotherapy and targeted therapy.Research DesignThis is a narrative review article that summarizes previous literatures regarding cervical cancer in terms of molecular mechanism, etiology, clinical developments, and prevention.Study SampleThe review encompassed studies from diverse sources, including experimental, observational, and clinical research published between 1992 and 2025.Data Collection and/or AnalysisData were collected through comprehensive literature searches using databases such as PubMed, Scopus, and the Cochrane Library with defined inclusion and exclusion criteria.ResultsNonetheless, there are gaps in research and controversies regarding vaccine coverage, screening practices, and treatment accessibility for poor populations. Precision medicine trends are emerging along with new biomarkers for early detection and personalized treatment, which also form part of this discussion. Key findings include the critical role of prevention measures in controlling the global impact of cervical cancer.ConclusionsThe paper synthesizes the existing knowledge and identifies gaps that require further research, which is significant in augmenting prevention, diagnosis, and treatment of cervical cancer towards addressing its public health implications worldwide.

Persistent human papillomavirus (HPV) infection is a causative agent for the majority of cervical cancer cases. The traditional Chinese medicine formula Quyoufang (QYF), a herbal oral decoction therapy, has been widely applied in the treatment of various diseases caused by HPV infection, but the molecular mechanism of QYF in the treatment of HPV infection remains unclear. This study aimed to investigate the effect of drug-containing serum of QYF on the apoptosis of HPV16-positive cervical immortalized epithelial cell line H8 in vitro.

Different concentrations of medicated serum were obtained by feeding QYF into the stomachs of rats. The effects of medicated serum on H8 cell proliferation and apoptosis were detected using the cell counting kit-8 assay (CCK-8) method, flow cytometry, and Hoechst 33342/PI apoptosis assays. The different expressions of E6, E7, p53, and pRb among H8 cells were detected by RT-PCR and Western Blot.

The results firstly indicated that the drug-containing serum of QYF induced apoptosis and suppressed the proliferation of H8 cells in a concentration-dependent manner. RT-PCR and Western Blot unveiled that in contrast to the control group, the QYF groups could markedly elevate the mRNA expression of P53 and pRb as well as promote the expression of p53 and pRb protein levels. The QYF groups suppressed the expression of E6 mRNA and inhibited the expression of E6 protein.

The drug-containing serum of QYF could effectively inhibit the proliferation of H8 cells and induce their apoptosis, possibly through the E6/p53-related pathway.

IntroductionThe utility and application of endocervical curettage (ECC) during colposcopy remain controversial. This study optimized ECC application for primary human papillomavirus (HPV) screening in patients with high-risk (HR)-HPV.MethodsThis retrospective study included patients with HR-HPV, who underwent subsequent cervical biopsy and ECC from January 1, 2014, to December 31, 2020. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The prediction model was presented as a nomogram and evaluated for discrimination and calibration.ResultsThe additional detection rate of cervical intraepithelial neoplasia 2 + lesions with ECC was 2.0% (77/3887) in patients with HR-HPV. In multivariate risk factor analysis, HPV 16 infection presented a high risk of positive ECC, followed by HPV 33, HPV 58, and HPV 31. Irrespective of the abnormal cytopathological results, positive ECC was significantly increased (all P < .001). Females with acetowhite changes on colposcopy, transformation zone (TZ) type II, TZ type III, colposcopic impression of high-grade squamous intraepithelial lesion, or cancer were at a high risk of positive ECC. The final prediction model included significant variables from risk factor analysis, and had excellent calibration and classification capabilities, with an area under the receiver operating curve of 0.902 (95% CI, 0.881-0.922). Additionally, calibration analysis suggested consistency.ConclusionAs the additional detection value of ECC is limited. A satisfactory prediction model was designed to optimize ECC application in patients with HR-HPV infection.

It is unclear what part KLF7 plays in cervical cancer. In this study, immunohistochemical and bioinformatics analyses reveal that KLF7 expression is lower in normal cervical tissues than in cervical cancer tissues, and the high level of KLF7 transcripts in cervical cancer tissues is negatively correlated with patients' overall and disease-free survival. In addition, KLF7 overexpression facilitates the proliferation, migration, and invasion of cervical cells, reduces PFKL expression, and increases the expressions of KLF4, Nanog, OCT4, CD44, SOX2, and ACADL. Additionally, knocking out the Exon 2 of KLF7 in HeLa cells results in a decrease in the total expression of KLF7 but an increase in the nuclear expression of KLF7, an increase in the capacity for proliferation, migration, invasion, and oncogenicity, and an increase in the density and ridge density of mitochondria. Consistent with these findings, RNA-seq analysis shows that knocking out the Exon 2 of KLF7 facilitates the expression of gene sets associated with cancer compared with that in wild-type HeLa cells. Moreover, the administration of alpha-lipoic acid (ALA) leads to a reduction in KLF7 expression in cells and tumor tissues, a suppression of the proliferation, migration, and invasion of HeLa and SiHa cells, and an increase in the carcinogenic potential of HeLa cells, while KLF7 overexpression shows the opposite effect on the expressions of ACADL and PFKL in HeLa and SiHa cells. In conclusion, KLF7 promotes the development of cervical cancer, and ALA can downregulate KLF7 expression and play a positive role in cervical cancer treatment.

The objective of this study was to develop liposomes (LP) containing a curcumin (CU) analog CA7 to enhance its pharmacokinetic profile and anti-cervical cancer (CC) effects.

Single-factor and Box-Behnken experiments were conducted to optimize the formulation of CA7-loaded liposomes (CA7-LP). The in vitro release, stability, biocompatibility, and pharmacokinetic of CA7-LP were evaluated. The biological effects of CA7-LP on Hela cells were assessed using MTT assays, colony formation assays, wound healing assays, and flow cytometry. Additionally, the anti-CC efficacy of CA7-LP was tested in mouse models of transplanted tumors.

The optimal formulation of CA7-LP exhibited a particle size of 92.43 ± 1.52 nm, a polydispersity index of 0.27 ± 0.01, an encapsulation efficiency of 97.79 ± 1.49%, a drug loading of 3.23 ± 0.20%, and a zeta potential of -6.69 ± 0.77 mV. Transmission electron microscopy confirmed that a spherical morphology was exhibited by CA7-LP. The cumulative in vitro release of CA7-LP was found to be 2.84 times greater than that of CA7, and stability at room temperature was maintained for at least 90 d. Furthermore, a significantly higher uptake of CA7-LP by Hela cells was observed compared to curcumin and CA7, leading to enhanced inhibition of cell proliferation, migration and cell cycle, as well as increased apoptosis (p < 0.05). In vivo studies revealed that CA7-LP exhibited superior pharmacokinetic properties compared to CA7 (AUC: 3.58-fold, Cmax: 5.65-fold, t1/2z: 1.2-fold). The anti-CC effects of CA7-LP were found to be comparable to those of Cisplatin injection, with a better safety profile.

The newly developed CA7-LP is considered a promising candidate for the treatment of CC, demonstrating high potential for clinical application.

Cervical cancer which is caused by persistent infection with oncogenic human papillomavirus (HPV), is the third most common cancer. HPV infection causes the progression of the normal cervix to cervical intraepithelial neoplasia (CIN) because it often occurs at the function conversion of the cervical squamous epithelium and columnar epithelium zone, further to invasive carcinoma. The difference in the ALDH1 expression was very significant. With the progression of cervical cancer, reports explained obviously increased nuclear and cytoplasm ALDH1 staining in comparisons of cervical carcinomas and normal cervix (P < 0.0001), cervical carcinomas compared with CIN (P = 0.0002). Therefore, ALDH1 as a stem marker, not only resists cervical cancer but also resists in normal cervix and CIN tissues. Developing an experimental method to discover cervical cancer earlier is feasible. Furthermore, the ALDH1 was expressed in human cervical cancer cell lines (Hela, SiHa, CaSki, HT-3, and C33A) together with western blot and immunocytochemical analysis. ALDH1 plays a significant role in nuclear and cytoplasm staining by immunochemistry in single or clustered HT-3 and C33A cells. However, western blot and immunochemical analysis did not detect ALDH1 in HeLa or CaSki, SiHa cells. We also discovered that there were no remarkable differences in age, tumor size, clinical TNM staging, multiple pelvic lymph node metastasis, or histological staging (p > 0.05) between the ALDH1-positive groups in 100 cervical cancer tissues. But after the control variable age, different ALDH rating survival function contrasted, it can be concluded that the higher ALDH1 scores with the survival of patients with the worse condition.

Co-infections with human papillomavirus (HPV) of multiple genotypes mainly occur due to increased sexual activity. To address the prevalence and trend of HPV co-infections in Japan, HPV-type-specific data from Japanese women (n = 8128) aged < 40 years and newly diagnosed with cervical abnormalities at 24 hospitals between 2012 and 2023 were analyzed. These included cervical intraepithelial neoplasia grade 1/2 (CIN1/2, n = 2745), CIN3/adenocarcinoma in situ (AIS) (n = 3953), and invasive cervical cancer (ICC, n = 1430). For women enrolled in this study since 2019, information on sexual behaviors was collected via a self-administered questionnaire. Time-trend analyses by disease category showed significant declines in the prevalence of multiple HPV infections in CIN1/2 (49.1%-38.3%, ptrend = 0.0004), CIN3/AIS (44.7%-31.5%, ptrend = 0.0002), and ICC (26.7%-10.5%, ptrend < 0.0001) during the last decade. When these data were analyzed separately for women aged 20-29 and 30-39 years, similar declining trends were observed in each disease category. Using data from 2111 women for whom information on sexual history was available, the number of sexual partners was strongly associated with increased multiple HPV infections (p < 0.0001). In conclusion, the declining prevalence of HPV co-infections in cervical cancer and its precursors may reflect a decrease in sexual activity among Japanese women of reproductive age.

Since its Fast-Track approval by the Federal Drug Administration, the human papillomavirus (HPV) vaccine has been marked by controversies. Unconfirmed reports of adverse events in both Japan and Denmark led to suspensions of national vaccination programs, which setback the fight against cervical cancer and associated mortality and morbidity. Despite follow-up studies of vaccine adverse reports, additional randomized control trials, and review reports from both the World Health Organization and the European Commission, there is still a great deal of hesitancy around the vaccine. While all three version of the HPV vaccine have been shown to be efficacious and safe, additional ethical dilemmas deserve to be considered as well.

The highly oncogenic human papillomavirus (HPV) is associated with numerous cancer types. While the role of viruses in the development of certain cancers is well established, the association between HPV infections and prostate cancer remains a subject of ongoing debate. This study aimed to investigate a potential association of prostate cancer with HPV infections utilizing a case-control study.

We extracted data from the Taiwan Longitudinal Health Insurance Database 2010. We retrieved 5137 patients with prostate cancer as cases and a 3:1 ratio of propensity score-matched patients without prostate cancer (15,411 patients) as controls. Multiple logistic regression analyses were carried out to scrutinize the association of prostate cancer with HPV infections while taking into account age, monthly income category, geographic location and urbanization level of the patient's residence as well as hyperlipidemia, diabetes, hypertension and chronic prostatitis, tobacco use disorder, and alcohol abuse/alcohol dependence syndrome.

The data indicate that out of all sampled patients, 1812 (8.8%) had a prior diagnosis of HPV infections before the index date. Among cases and matched controls, HPV infections were diagnosed in 743 (14.5%) and 1069 (6.9%) patients, respectively. The results from the chi-square test demonstrate that individuals with prostate cancer exhibited a significantly higher incidence rate of HPV infections than their control counterparts (p < 0.001). Furthermore, in comparison to controls, individuals with a history of HPV infections had an adjusted odds ratio of 2.321 (95% CI: 2.097~2.568) for developing prostate cancer. Notably, individuals diagnosed with chronic prostatitis were also more likely to be subsequently diagnosed with prostate cancer (adjusted odds ratio=1.586; 95% CI = 1.338~1.879), which aligns with expectations in this context.

We found prostate cancer to be significantly associated with HPV infections, contributing to the mounting body of evidence indicating a plausible connection between the two.

The majority of women in low- and middle-income countries have low awareness of cervical cancer. This study sought to establish awareness of cervical cancer risk factors and preventive approaches, as well as sources of information and perceived causes of cervical cancer among secondary school girls in northern Uganda.

This was a cross-sectional study conducted in rural northern Uganda. We collected data using an investigator administered pre-tested questionnaire. Analysis was done with STATA version 14.0. Multivariate analyses with logistic regressions models were used to determine magnitudes of association between independent and outcome variables. Odds ratios and accompanying 95% confidence intervals are reported. Statistical significance was considered if the two sided p-value <.05.

Most participants (97%; n = 624) had heard of cervical cancer before this study. The most common source of information about cervical cancer was friends (31.1%; n = 194). More than half of the participants (59%; n = 380) had heard about a vaccine that prevents cervical cancer, but only a third (33%; n = 124) had ever received a dose of the vaccine. The majority of participants (89%; n = 550) reported that cervical cancer could be prevented; however only half (52%; n = 290) knew that vaccination of girls aged 9-13 years could prevent cervical cancer. The majority of participants did not recognize the risk factors for cervical cancer; for example, only 15% (n = 98), 7% (n = 45), and 1.4% (n = 9) recognized early onset of sexual intercourse, infection by the human papillomavirus (HPV), and smoking respectively. On adjusting for age, students' class, and religion, students in schools with school health programs were twice (aOR = 2.24: 95%CI; 1.24-4.06) more likely to know that cervical cancer is preventable.

Secondary school girls need information on cervical cancer risk factors and approaches to prevention so that they may avoid exposures to the risk factors and promptly seek and undertake preventive approaches including HPV vaccinations.

We explored the prevalence of human papillomavirus (HPV) infection among women in Jinshan District, Shanghai.

We analyzed all HPV testing samples sent from our unit between December 2023 and April 2024. We reported the HPV prevalence overall, by age, and by subtype.

In total, 3788 women aged 16 to 90 years had HPV test results. The prevalence of infection with any HPV subtype was 17.9%. The HPV prevalence by age group was: ≤30 years, 15.4%; 31-40 years, 14.7%; 41-50 years, 17.0%; 51-60 years, 22.4%; >60 years, 31.0%. Among HPV-positive women, 80.6% had infection with one subtype, 16.4% had dual infection, and 3.1% had three or more subtypes detected. We found 640 cases (16.9%) of infection with high-risk HPV subtypes and 139 cases (5.04%) of infection with low-risk HPV subtypes. The most common high-risk subtypes were HPV 52, 53, 58, and 16; the most common low-risk subtypes were HPV 81, 70, and 42.

We detected ≥1 HPV subtype among most women in our study. The prevalence of HPV was lowest in younger women and highest in women age >60 years. Tailored strategies for older women are needed to prevent HPV infection and cervical cancer.

Human papillomavirus (HPV) prophylactic vaccines were first licensed in 2006 with the primary goal of preventing HPV-related cancers, with cervical cancer accounting for the highest morbidity and mortality globally. Six HPV vaccines have been licensed; 4 of these have been prequalified by the World Health Organization, and additional products are in the pipeline. This article provides an overview of HPV vaccine coverage and current and anticipated vaccine supply vs expected demand. Given that the 2022 World Health Organization position paper on HPV vaccines includes a 1-dose regimen as an alternate schedule, we will discuss the evidence for using licensed vaccines in single-dose regimens and the approach to generating similar supportive data for other current and future vaccines. The broad adoption of a single-dose HPV vaccine regimen would expand access to vaccines by improving the supply-demand balance, increasing affordability, and simplifying logistics, which will ultimately impact HPV-related morbidity and mortality.

Human Papillomavirus (HPV) is a widespread infection associated with various cancers, including cervical, oropharyngeal, anal, and genital cancers. This infection contributes to 5 % of global cancer cases annually, affecting approximately 625,600 women and 69,400 men. Cervical cancer remains the most prevalent HPV-linked cancer among females, with the highest incidence seen in low and middle-income countries (LMICs). While most HPV infections are transient, factors such as HPV variants, age, gender, and socioeconomic status influence transmission risks. HPV is categorized into high-risk (HR-HPV) and low-risk types, with strains like HPV 16 and 18 displaying distinct demographic patterns. The intricate pathogenesis of HPV involves genetic and epigenetic interactions, with HPV oncogenes (E6 and E7) and integration into host DNA playing a pivotal role in driving malignancies. Early diagnostics, utilizing HPV DNA testing with surrogate markers such as p16, and advanced molecular techniques like PCR, liquid biopsy, and NGS, significantly impact the management of HPV-induced cancers. Effectively managing HPV-related cancers demands a multidisciplinary approach, including immunotherapy, integrating current therapies, ongoing trials, and evolving treatments. Prevention via HPV vaccination and the inclusion of cervical cancer screening in national immunization programs by conventional Pap smear examination and HPV DNA testing remains fundamental.Despite the preventability of HPV-related cancers, uncertainties persist in testing, vaccination, and treatment. This review article covers epidemiology, pathogenesis, diagnostics, management, prevention strategies, challenges, and future directions. Addressing issues like vaccine hesitancy, healthcare disparities, and advancing therapies requires collaboration among researchers, healthcare providers, policymakers, and the public. Advancements in understanding the disease's molecular basis and clinical progression are crucial for early detection, proper management, and improved outcomes.

The host transcription factor p53 is a critical tumor suppressor in HPV-induced carcinogenesis, regulating target genes involved in cell cycle arrest and apoptosis. However, the p53 targets have not been thoroughly analyzed in HPV-infected cells. In this study, p53 signaling in HPV16 and HPV18 cells was activated by depleting the viral oncoprotein E6. Subsequently, p53-regulated genes were identified by comparing them with genes altered in p53-silenced cells. True p53 targets were defined as genes with at least one overlapping p53 binding site and ChIP peak near their locus. Our analysis revealed that while some p53 targets were common to both the HPV16 and HPV18 cells, the majority of the targets differed between these two types, potentially contributing to the varying prevalence of HPV16 and HPV18 in cervical cancer. Additionally, we identified SCN2A as a novel p53 target involved in p53-induced cell cycle arrest in HPV-related carcinogenesis. This study provides new insights into the mechanisms by which p53 inhibits HPV-induced carcinogenesis.

The increasing trend of cervical cancer in women in their 20s in Japan is largely attributable to the low rate of cervical cancer screening. This study aimed to assess the usefulness of human papillomavirus (HPV) self-sampling among 24-year-old Japanese women who had never previously been screened for cervical cancer during the coronavirus disease (COVID-19) pandemic.

In August 2021, consenting eligible women received HPV self-sampling kits. An Evalyn brush was used for self-sampling, and a Cobas 4800 PCR-based HPV DNA test was used to detect high-risk HPV genotypes. We analyzed the return rates of self-sampling kits and conducted a survey on the acceptability of the self-sampling method.

Of the total 1997 eligible women, 13.4% (268/1997) agreed to participate. The return rate of the kits was 72.4% (194/268), corresponding to 9.7% of the eligible population. Among the participants who returned the kits, 14.9% (29/194) tested positive for HPV, and 41.4% (12/29) of these underwent subsequent cytological testing. The questionnaire results indicated that 57.8% of participants reported no pain during self-sampling, and 72.9% expressed a willingness to continue using the self-sampling method in the future.

This study demonstrated that opt-in HPV self-sampling among 24-year-old women who had never been screened for cervical cancer had a favorable kit return rate and was well accepted by the participants, especially during the COVID-19 pandemic. However, the follow-up cytology test rates were low, highlighting the need for improved post-screening management.

This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020.

This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix.

Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears.

In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

Oncogenic viruses such as, Human papillomavirus (HPV) associated head and neck cancers have been considered to represent different etiological and pathological behaviour. This pilot study was conceived to investigate high risk HPV (hr-HPV) infection and its association with life style habits such as tobacco, alcohol consumption in patients with hypopharynx cancer from North -East India. A total of thirty four primary hypopharynx cancer biopsy specimens were collected. These samples were analysed for hr-HPV DNA using nested multiplex PCR (NMPCR). The lifestyle and dietary associated factors were collected through a self- designed questionnaire. The presence of hr-HPV was confirmed in 50% (n = 17) patients with hypopharynx cancer by nested multiplex PCR (NMPCR). Among hr-HPV positive cases, only HPV- 16 genotype was found. Significant association was observed between hr-HPV infections with alcohol consumption (p-0.025), alcohol with tobacco habit (p-0.01). Our study demonstrated that alcohol consumption, tobacco chewing may act as risk factors for hr-HPV infection in a subset of patients with hypopharynx cancer from the North-East region of India.

Sexually transmitted infections (STIs) and human papillomavirus (HPV) infections are common among women of reproductive age and can lead to infertility, adverse pregnancy outcomes, neonatal infections and cervical cancer. In countries with limited medical coverage, untreated infections contribute to high morbidity. This study aimed to expand the current knowledge on the prevalence of bacterial vaginosis (BV) and STIs in pregnant Ethiopian women and assess the association of these conditions with HPV infections. Socio-demographic data and vaginal lavage samples were collected from 779 asymptomatic women aged 18 to 45 years (median age, 25.9 years) attending antenatal care in seven centres across Ethiopia. Multiplex polymerase chain reaction was used to test for BV, Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, herpes simplex virus types 1 and 2 (HSV-1/2), Mycoplasma, Ureaplasma, Candida species and HPV. Overall, 26.8% (95% confidence interval (CI): 23.7-29.9) of women tested positive for BV or one of the following STIs: C. trachomatis, T. vaginalis, N. gonorrhoeae, Mycoplasma genitalium, HSV-1/2 or Ureaplasma urealyticum. Additionally, 22.1% tested positive for at least one high-risk HPV type. Chlamydia trachomatis and HSV-2 were significantly more common among women who were positive for HPV and high-risk HPV. This study reveals a high prevalence of asymptomatic pregnant women who are positive for BV, STIs or HPV, putting them at risk of adverse pregnancy outcomes, secondary infertility or cervical cancer in a country with limited medical coverage. Screening and treating these women could be crucial in reducing morbidity.

This systematic literature review aims to summarize global research on parental acceptance, attitudes, and knowledge regarding human papillomavirus vaccinations.

The literature search was conducted in PubMed, Web of Science and Scopus, and included publications from 2006 to 2023. Study quality was assessed using the Newcastle-Ottawa Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Meta-analyses were performed using random-effects models to estimate pooled parental acceptance of HPV vaccinations. Studies were stratified by study years, and a subgroup analysis was conducted to estimate vaccine acceptance rates by world regions. Additionally, sensitivity analyses examined the role of parents in accepting HPV vaccinations for children of different sexes.

Based on 86 studies, we found that parents generally supported HPV vaccinations for their children, yet HPV vaccine acceptance rates showed high variation (12.0 to 97.5%). The subgroup analysis revealed geographical variations in pooled parental HPV vaccine acceptance rates, with the highest rate observed in Africa (79.6%; 95% CI: 73.5-85.2; I² = 98.3%; p < 0.01) and the lowest in North America (56.7%; 95% CI: 49.3-64.0; I² = 99.4%; p < 0.01). Sensitivity analyses showed that acceptance was higher for daughters than for sons, with mothers more willing to get their daughters vaccinated. The proportion of parents reporting barriers or benefits regarding HPV vaccinations varied widely (0.3-95.8%) between study regions. Across all world regions, fear of adverse effects and concerns about vaccine safety were the main barriers, whereas the desire to protect their children from cancer was a significant predictor of vaccine acceptance. Knowledge levels varied widely (6.5 to 100%) between world regions and according to the questions asked. In most studies, knowledge e.g., that HPV is sexually transmitted, and that HPV vaccination provides protection against cervical cancer, ranged from moderate to high.

The results indicated moderate parental acceptance of HPV vaccines. Public knowledge of HPV infection should be promoted, and special efforts should be made to minimize the existing barriers and increase vaccination accessibility and uptake.

In this study, we characterized the HPV genotype distribution in a population of 489 adults already positive for HPV DNA. The study population was divided into two groups: 244 HIV-positive (HIV+) men who have sex with men (MSM) undergoing routine anal screening for sexually transmitted diseases (STDs) and 245 women undergoing routine cervical cancer screening. Acknowledging the fact that women and MSM represent two independent circles of sexual practices, which are-largely-exclusive of each other, we were interested in determining if particular genotypes of human papillomavirus (HPV) disproportionately predominate in one of these circles compared to the other.

HIV+ MSM are significantly more likely to be infected with multiple genotypes at a time, with an odds ratio (OR) of 9.30 (95% confidence interval [CI]: 3.91-22.1) and a p-value of <0.001. In addition, multivariable-adjusted logistic regression analysis showed that anal swab samples were significantly more likely to harbor lrHPV infections, with an OR of 6.67 (95% CI: 2.42-18.4) and a p-value of <0.001, in particular, HPV 6, with an OR of 8.92 (95% CI: 3.84-20.7) compared to cervical samples of screening women.

Given the significant impact of recurrent anogenital warts (AGWs) on quality of life and the accompanying predisposition to invasive anal cancer, our data underscore the critical need for HPV vaccination. This includes expanding vaccination eligibility to include both boys and adults within high-risk populations.

Data on the patterns of single and multiple HPV infections are largely limited to small size studies, and the regional difference have not been systematically examined.

A literature search was conducted using PubMed, Embase, and Web of Science databases up to Sept 22, 2023. The pooled prevalence of HPV infection were calculated using random-effects meta-analysis. Subgroup analysis was used to explore the heterogeneity, and publication bias was evaluated by Egger's test and Begg's test.

There were 121 studies included with 1,682,422 participants. Globally, the most common genotypes of single HPV infection were HPV16 (7.05 %), 18 (1.94 %), 52 (1.93 %), 58 (1.68 %), and 31 (1.53 %), as well as HPV 16 (4.91 %), 31 (2.68 %), 52 (2.20 %), 51 (1.99 %), and 18 (1.96 %) in multiple HPV infections. Apart from HPV16 and 18, HPV52 and 58 were common in Asia, HPV31 and 51 was in Europe, North and South America, and HPV35 and 45 were in Africa. The prevalence of HPV infection among different age groups (<30, 30-50, >50 years age groups) was 20.93 %, 16.27 %, and 18.69 %, respectively. The single HPV infection prevalence in the No-ILs, LSILs, HSILs, and cervical cancer groups were 16.17 %, 51.60 %, 57.12 %, and 62.88 %, respectively, as well as in multiple infections were 5.09 %, 30.93 %, 32.86 %, and 21.26.

Developing local HPV vaccines is necessary based on the HPV infection pattern. It is essential to educate young women to get vaccinated and encourage elderly women to have regular cervical cancer screenings to reduce the danger of cervical cancer.

Cervical cancer (CC) is one of the highest prevailing causes of female cancer-related mortality globally. A significant discrepancy in incidence has been noted between high and low-middle-income countries. The origins of CC have been accredited to the human papillomavirus (HPV) with serotypes 16 and 18 being the most prevalent. HPV vaccines, with 90%-97% efficacy, have proven safe and currently function as the primary prevention method. In addition, secondary prevention by timely screening can potentially increase the 5-year survival rate by >90%. High-precision HPV DNA testing has proven to be both highly sensitive and specific for early detection and is advocated by the WHO. Lack of public awareness, poor screening infrastructure and access to vaccines, socio-cultural concerns, along with economic, workforce-associated barriers and the presence of marginalised communities unable to access services have contributed to a continued high incidence. This article comprehensively analyses the efficacy, coverage, benefits and cost-effectiveness of CC vaccines and screening strategies including the transition from cytological screening to HPV self-sampling, while simultaneously exploring the real-world disparities in their feasibility. Furthermore, it calls for the implementation of population-based approaches that address the obstacles faced in approaching the WHO 2030 targets for CC elimination.

Wilms' tumors are pediatric renal tumors that generally have a good prognosis and outcomes. Viral illnesses have been linked to development of neoplasms and should be considered as a factor that could modulate overall survival.

We considered recently developed adaptive immune receptor, genomics and bioinformatics approaches to assess the potential impact of cytomegalovirus (CMV) infections in Wilms' tumor.

T-cell receptor (TCR) complementarity determining region-3 (CDR3) amino acid sequences from Wilms' tumor specimens represented by the Therapeutically Applicable Research to Generate Effective Treatments dataset were compared with known anti-CMV TCR CDR3s, indicating that cases representing the anti-CMV TCR CDR3s had worse outcomes. Then, a chemical complementarity scoring approach for the Wilms' tumor, TCR CDR3s and a series of CMV antigens further indicated that cases representing a higher chemical complementarity to the CMV antigens had worse outcomes.

Overall, we present a potentially novel method to assess CMV infections and identify patients who could benefit from therapies that address such infections.

Introduction Recently, the expression of metallophosphoesterase-domain-containing protein 2 (MPPED2) was identified in cervical cancer. However, its precise role and correlation with other tumor suppressor proteins, such as p16INK4A, is not well studied in high-risk human papillomavirus (HPV) integrated human cervical carcinoma. Hence, in the present study, we try to see the expression of MPPED2 in human cervical carcinoma and its correlation with age and p16INK4A protein expression level. Methods The prospective study consists of 200 samples of 150 known cervical carcinoma and 50 controls. Histopathological evaluation, immunohistochemical staining, and semi-quantitative scoring of the intensity of proteins were performed. Statistical analysis was performed with the Shapiro-Wilk test, Spearman's rho correlation sig. (two-tailed), and Student's t-test. Results The data show that among the 150 cases, 136 (68.0%) cervical carcinoma tissues express the presence of high-risk HPV viral genome integration in the host cell. The expression of p16INK4A protein is higher in those tissues identified with high-risk HPV viral genomes. In contrast, the expression of MPPED2 protein is lesser or absent in those cervical tissues that have the higher expression of p16INK4A protein and vice versa. There is a significant correlation (p=0.000) between age and p16INK4A protein expression but not with MPPED2. A significant linear correlation (p=0.000) is found between the p16INK4A and MPPED2 proteins. Conclusion It may support the therapeutic application of MPPED2 protein to prevent cervical carcinoma progression in the near future.

Background: Few studies have analyzed the effect of matrix metalloproteinase (MMP) expression patterns on the tumor microenvironment (TME) during development of cervical cancer (CC). Methods: We elucidated the landscape and score of MMP expression in CC using single-cell RNA sequencing (scRNA-seq) and RNA sequencing datasets. Further, we aimed the MMPscore to probe the infiltration of immune cells. Further, MMP expression was measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Results: We found MMPs were cell-type specific expressed in diverse types of CC cells, regulating the relative pathways of CC progression. Two distinct MMP expression patterns that associated infiltrated tumor microenvironment (TME) were identified. We discovered MMP expression patterns can predict the stage of tumor, subtype, stromal activity in the TME, genetic variation, and patient outcome. Patients with high MMPscore benefited from significantly better treatment and clinical outcomes. Conclusion: These results indicate high MMPscore in diverse cell types may regulate immune response and improve the survival of patients with CC, which assist in developing more effective immunization strategies.

High-risk human papillomavirus (HPV) infection is associated with cervical cancer while low-risk HPV strains mostly cause benign lesions. Multiple studies have also associated HPV with coronary artery (CAD) disease in women. Furthermore, the climacteric period in women, triggers chronic inflammation and has major implications for CAD and associated lipid disorders. The association of HPV with coronary artery disease in climacteric women has few studies, and the objective of this review is to gather and analyse scientific data on the subject. This is an integrative review performed on PubMed and Google Scholar using the keywords "HPV", "coronary heart disease" and "climacteric", among these keywords the boolean operator AND and the publication date filter. (2018 onwards). Five articles were found, whose main results show presence of high-risk vaginal HPV in climacteric women. Climacterium and HPV were associated with a three-fold increased risk of CAD, as well as with factors related to menopause that promote atheroma formation, lipid disorders and chronic inflammation. Thus, these results support the association between HPV infection and CAD in climacteric women, possibly via chronic inflammation, hormonal factors related to menopause and dyslipidemia.